Infant animals have the ability to respond in age-specific ways to threatening stimuli. Little is known, however, about the neural substrate underlying adaptive fear-like responses. The prefrontal cortex plays a major role in the regulation of emotion in adult animals. In particular, the medial part of the prefrontal cortex modulates behavioral responses to threat through projections to the amygdala and the periaqueductal gray. The objective of this application is to determine the role of the medial prefrontal cortex and its projection areas in adaptive responses to threat in young animals. The central hypothesis is that subdivisions of the medial prefrontal cortex modulate emotional behavior across early development by either facilitating fear-like responses to threat or by inhibiting fear-like responses to non-threat. To test this hypothesis, young rats of three different ages are exposed to age-specific threatening and non-threatening situations and the role of the medial prefrontal cortex and its projection areas in fear-like responses to these situations is determined. There are three specific aims. 1. Subdivisions of the medial prefrontal cortex are pharmacologically inactivated and effects on behavioral responses to threat and non-threat are determined. Medial prefrontal cortex output function is determined by assessing activation in its projection areas, the amygdala and the periaqueductal gray. Neuronal activation is assessed by immediate early gene expression. 2. Subdivisions of the medial prefrontal cortex are stimulated and effects on behavioral responses to threat and non-threat and on the activation of amygdala and periaqueductal gray are assessed. 3. To determine the neural basis of differential responsivity at the three ages, the activation of GABAergic interneurons in subdivisions of the medial prefrontal cortex by threatening and non-threating situations is assessed. The proposed study will provide strong evidence for the dual role of the medial prefrontal cortex in emotion regulation across early life. Understanding prefrontal cortex function in development is crucial because early alterations of prefrontal cortex circuitry are associated with increased risk for the development of psychopathologies such as anxiety disorders later in life.